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Stereochemical basis for the anti-chlamydial activity of the phosphonate protease inhibitor JO146
No full textJO146, a mixture of two diastereomers of a peptidic phosphonate inhibitor for Chlamydial HtrA (CtHtrA), has reported activity against Chlamydia species in both human and koala. In this study we isolated the individual diastereomers JO146-D1 and JO146-D2 (in > 90% purity) and assessed their individual inhibitory activity against the serine protease human neutrophil elastase (HNE) which is structurally related to CtHtrA, as well as in Chlamydia trachomatis cell culture. JO146-D2 [S,S,R-Boc-Val-Pro-ValP(OPh)2], the isomer with the physiologically relevant valine at P1, had an approximate 2.5-fold in-crease in in vitro HNE inhibition potency over JO146-D1 [S,S,S-Boc-Val-Pro-ValP(OPh)2] and greater than 100-fold increase in cellular anti-chlamydial activity compared to JO146-D1 which possesses the unnatural valine at P1. JO146 and the individual diastereomers had excellent selectivity for the serine protease HNE over the potential off-target serine proteases trypsin and chymotrypsin. Docking studies supported the biological data with a geometrically unfavoured interaction observed between the P1 valine residue of JO146-D1 and the enzyme S1 sub-pocket.Peer Reviewe
Freshwater and Planning: An Analysis of the NPSFM
Get PDFWithin New Zealand, water is utilized and valued for a diverse range of reasons. Values differ according to region, whether the prominent uses are urban drinking water, hydroelectricity, irrigation, or cultural values, each has a different and sometimes contrasting understanding of water and how it should be used. Contestation and conflict arise over freshwater as quality declines and waterways become over-allocated, causing these viewpoints to compete. The management framework for freshwater is created under the Resource Management Act. Since its passing, and despite its core principle of sustainability, freshwater bodies have ironically deteriorated. Inadequate management of human use occurring within catchments and disregard for future uses in terms of water allocation have impacted our waterways. In response, the Central Government created the National Policy Statement on Freshwater Management (NPSFM), which is the primary focus for this research.
The National Policy Statement for Freshwater Management informs lower order policy and planning documents to create national direction for an issue of national significance. The aim of this research is to assess how effective a National Policy Statement is in improving water quality and management at a regional level for freshwater bodies in New Zealand. To assist the analysis, a comparison between the Southland and Auckland freshwater management contexts was done. The methods used to obtain data for this research include a literature review and semi-structured interviews. Interviews were conducted with relevant stakeholders, including representatives of catchment groups, public and private planners, water strategy managers, mana whenua and other key stakeholders.
The findings show the NPSFM sits at an institutionally high level and affects freshwater management slowly through the planning framework. Two of the most influential policy directions are the introduction of environmental limits and Te Mana o te Wai, which induce catchment wide planning, consideration of the environment as a user of water, and draw decisions makers attention to the effect activities have outside of the water management framework. Efficacy and capacity of Regional Councils is critical in implementing the NPSFM which is further determined by the social, economic and geographical settings of regions. Implications are felt more strongly in regions with less proactive freshwater planning, higher amounts of agricultural activities and less institutional capability. There are no obvious direct benefits to certain stakeholders; however, there are indirect benefits for iwi participation in decision making and the incorporation of Māori values into regulatory frameworks. Southland is heavily reliant on agricultural practices and the impacts for farmers are clear, while Auckland is now required to meet national bottom lines irrelevant to urban catchments. This has increased with the introduction of a National Environmental Standards for Freshwater in 2020 which have further targeted policy at agricultural activities, prompting impacts for livelihoods and land values.
Overall, the NPSFM has enacted a change at a fundamental level, through the use of planning processes critical adjustments are applied to the water management framework, effectively changes in water quality occur over a generational time period
Graph-structured populations and the Hill–Robertson effect
Get PDFThe Hill–Robertson effect describes how, in a finite panmictic diploid population, selection at one diallelic locus reduces the fixation probability of a selectively favoured allele at a second, linked diallelic locus. Here we investigate the influence of population structure on the Hill–Robertson effect in a population of size N. We model population structure as a network by assuming that individuals occupy nodes on a graph connected by edges that link members who can reproduce with each other. Three regular networks (fully connected, ring and torus), two forms of scale-free network and a star are examined. We find that (i) the effect of population structure on the probability of fixation of the favourable allele is invariant for regular structures, but on some scale-free networks and a star, this probability is greatly reduced; (ii) compared to a panmictic population, the mean time to fixation of the favoured allele is much greater on a ring, torus and linear scale-free network, but much less on power-2 scale-free and star networks; (iii) the likelihood with which each of the four possible haplotypes eventually fix is similar across regular networks, but scalefree populations and the star are consistently less likely and much faster to fix the optimal haplotype; (iv) increasing recombination increases the likelihood of fixing the favoured haplotype across all structures, whereas the time to fixation of that haplotype usually increased, and (v) star-like structures were overwhelmingly likely to fix the least fit haplotype and did so significantly more rapidly than other populations. Last, we find that small (N< 64) panmictic populations do not exhibit the scaling property expected from Hill & Robertson (1966 Genet.Res. 8, 269–294
Let's talk: Investigating adult-child interactions within the home-literacy environment to better support children's developing oral language and early-literacy skills
No full textEarly successes in reading lead to further successes over time, whereas early struggles with reading limit future learning (Stanovich, 1986). Therefore, to help avert this achievement gap, the primary aim of this thesis was to investigate a variety of adult-child interactions in the home that help develop the precursors to independent reading: children’s oral language and early-literacy skills.
Study one compared meaning- and code-focused talk in rhyming versus non-rhyming picturebooks in relation to children’s oral language and early-literacy skills. Forty-five parents were audio-recorded reading two picturebooks, one rhyming and one non-rhyming, with their preschool-aged children. Children’s concurrent oral language and early-literacy skills were also assessed. Parents made higher proportions of inference/predictions in the non-rhyming book, and higher proportions of print- and sound-focused talk in the rhyming book. Further, parents’ meaning-focused talk predicted children’s concurrent oral language skills, and parents’ code-focused talk (both print- and sound-focused) predicted children’s concurrent early-literacy skills. These associations differed by book style and were moderated by children’s age, such that parents’ print-focused talk in the rhyming book was positively associated with early-literacy skills only for older children.
Study two investigated the comparative effects of two novel shared reading conditions and a non-shared reading control on parent-child extratextual talk, reminiscing, and children’s oral language and early-literacy development. Two of the conditions were preventive interventions, Rich Reading and Reminiscing (RRR; n = 24)) and Strengthening Sound Sensitivity (SSS; n = 23), and one was an Activity-Based Control (ABC; n = 24). Both preventive interventions included workshops on the benefits of interactive shared-reading and post-reading activities to further consolidate learning; however, they each targeted different oral-language and early-literacy skills. RRR targeted children’s vocabulary development and story comprehension through comments and questions about the storyline, new words, and character’s emotions during shared reading, as well as post-reading elaborative reminiscing based on themes within the books. Conversely, SSS targeted children’s phonological awareness through comments and questions about the sounds of words during shared reading, as well as post-reading singing and sound-play. To control for book-specific effects, families in both conditions received the same set of 12 picturebooks embedded with condition-specific prompts. Alternatively, families in the ABC condition received tip sheets and materials for developmentally-appropriate structured play. We invited participating families to complete two interaction activities at pre- and post-test: shared book-reading and reminiscing. We also assessed children’s vocabulary, story comprehension, phonological awareness, and alphabet knowledge at both time points. Overall, participation in RRR positively predicted parents’ total on-topic and meaning-focused talk during the post-test shared reading task, whereas participation in SSS positively predicted parents’ and childrens’ print- and sound-focused talk. Similarly, during the post-test reminiscing task, participation in RRR positively predicted parents’ total elaborations and confirmations. Finally, there were no statistically significant main effects of condition for children’s oral language and early-literacy skills. Instead, relations between condition and post-test letter naming fluency were moderated by child age, such that participation in either book-reading condition was associated with higher post-progam letter recognition for older preschool children.
Study three extended study two, in that we investigated the comparative effects of RRR, SSS, and ABC on parents’ beliefs. We also invited families to evaluate the three conditions to assess social validity. Participating parents filled out questionnaires pre- and post-participation measuring their satisfaction, interest, and sense of self-efficacy in relation to parenting, as well as their literacy beliefs and situational-specific self-efficacy. Parents were also invited to rate their own and their child’s enjoyment of project activities, along with evaluative statements about participation. Overall, parents in all three conditions reported high levels of enjoyment for both themselves and their children. Parents in all three conditions also reported that that they: noticed their children developing new skills, felt more confident about helping their children get ready for school, felt that their children were better prepared, and would recommend their respective condition to other parents. Parents in the RRR and SSS conditions also reported developing new skills. However, condition did not contribute to the regression model for any post-test parent belief variables, over and above parent education and the applicable pre-test belief scores. Instead, there were statistically significant moderator effects as functions of parent education and percentage of project activities implemented across the six week period.
Overall, this thesis demonstrates that: (a) rhyming picturebooks may elicit a higher proportion of code-focused talk, and non-rhyming picturebooks may elicit a higher proportion of meaning-focused talk; (b) print-focused talk may be more useful for older than for younger pre-schoolers; (c) both RRR and SSS may be effective and enjoyable preventive interventions for enhancing parents’ and children’s decontextualised talk during shared book-reading and reminiscing; and (d) home-based parent education programmes may have less of an immediate impact on parents’ reading beliefs and self-efficacy than previously thought
Circulating biomarkers and prognosis in colorectal cancer
Get PDFColorectal cancer is an important global health problem as the second most common cause of cancer deaths worldwide. The ability to risk-stratify patients according to predicted outcome is fundamental to patient management and historically the TNM staging system has formed the basis for this. As more is becoming understood about the role of the host’s immune response on cancer progression and its influence on outcome, there is a growing need to evaluate the potential role of circulating inflammatory cytokines as prognostic markers in colorectal cancer.
In chapter Two, the patterns of disease recurrence were evaluated in a cohort of 237 patients. Recurrences were observed most frequently within two years of surgery and at distant sites. The prognostic value of pre-treatment carcinoembryonic antigen (CEA), as the most widely used circulating prognostic biomarker, was also evaluated in a subset of this cohort. We found it to be predictive of overall and disease free survival, independent of TNM stage and through these findings, we established CEA as a benchmark against which novel approaches could then be compared.
Chapter Three comprises a systematic review whereby seven studies were found to evaluate the prognostic value of multiple cytokine analysis. A combined cytokine score was utilised in four studies although the individual cytokines used and the methods by which they were combined varied between studies. Some promise was shown by applying a multi-marker approach to circulating cytokines.
Chapters Four and Five were prospective studies. In Chapter Four, IL-6, IL-8, IL-1β and TNFα plasma levels were compared between subjects who were recruited into three groups: healthy controls, stage II disease and stage IV disease. Plasma IL-6 and IL-8 were found to differ significantly between patients with stage IV disease and those without. Furthermore, when a combined IL8-CEA score was developed, the ability to distinguish between the three groups was enhanced, compared to any individual marker. In Chapter Five, we went on to evaluate the prognostic value of circulating cytokine markers in a longitudinal study. A panel of eight cytokines was selected, each with a foundation in experimental data linking their actions to colorectal cancer progression. These cytokines were measured in a cohort of 73 patients with non-metastatic colorectal cancer, including the combination of IL8 and CEA, developed in Chapter Four. Following a median duration of 18 months, combined scores composed of IL-8 and IL-10, when combined with CEA, were shown to improve marginally upon CEA alone in risk-stratifying the cohort by disease free survival. A number of limitations to the study were acknowledged including a relatively small sample size and short follow-up duration, preventing the feasibility of a multi-variate survival analysis.
Whilst we found a multi-marker approach, combining circulating inflammatory cytokines with CEA, to offer some promise in colorectal cancer prognostication, further study is necessary to evaluate the IL10-CEA score in a larger study sample over a five year follow-up duration
Collaborative freshwater management in the Hurunui-Waiau Zone, North Canterbury: Progress of the Canterbury water management strategy (CWMS)
Get PDFThe planning and management of freshwater resources is crucial in intensively farmed areas, particularly where rainfall is erratic and there can be serious shortages for both irrigation and livestock. The Canterbury region on the eastern side of New Zealand’s South Island is one of the country’s most important agricultural areas, which in the last two decades has experienced widespread conversions to dairy farming alongside periods of drought. Concerns about water quality and disputes over water resources were key factors in the formulation of the Canterbury Water Management Strategy (CWMS), a collaborative approach to freshwater management. Such approaches are an increasingly popular response to dealing with complex resource management issues. This thesis focuses on the implementation of the CWMS in the Hurunui- Waiau Zone in north Canterbury. Drawing upon detailed field-based research among a range of stakeholders with different values and interests the complexity of freshwater management was revealed. While some significant progress has been made, there are some concerns about the effectiveness of the collaborative approach. The thesis concludes with a number of recommendations for the ongoing implementation of the CWMS. The research also has wider relevance across the Canterbury region and in other areas which are attempting to address freshwater management issues
Long-term outcomes of cruciate ligament injury: matched cohort analysis of New Zealand linked register data
No full textExamining the changing representations of family relations: Insights from leisure photographs
No full textTaking photographs is an inseparable part of life for many families. Families were (and still are) interested in taking photos of their growing children, special rituals and ceremonies, and family gatherings. As tangible records of family life and relationships, family leisure photographs illustrate broader societal changes and document multiple aspects of members’ lives. Therefore, the aim of this research is to explore the changing representations of family life and relationships through leisure photographs in light of societal changes over time.
The aim of this thesis necessitated a longitudinal analysis. Therefore, archival photographs were chosen as the data source for the study. In New Zealand, the University of Otago Hocken Collections in Dunedin has a rich archive of family photograph albums that are available for viewing by researchers and members of the public. These albums only cover the period 1896 to 1955, so advertising and snowball sampling was used to gain access to material from 1955 to 2018. Family photograph albums were collected in both hard and digital forms. A total of 58 hard copy photograph albums and 125 digital photograph albums (all private family albums) spanning the period 1896 to 2018 were collected and ultimately 4700 family leisure photographs were analysed using visual thematic analysis.
The findings are presented in the form of three separate papers. All papers are self-contained and focus on the same research context (New Zealand), using the same analytical technique (visual thematic analysis) to analyse the same dataset. While these three papers utilise the same set of data, they draw from discrete fields of literature to answer different questions.
In examining the changing representations of fatherhood, the first paper shows that family leisure photographs reflect a shift away from father as an invisible breadwinner in the early twentieth century, to participating in leisure consumption with the family in the post-war years, to visible and involved during the women’s liberation movement of the 1960s and 1970s, to the position of playmate-teacher in more recent decades. It provides evidence that fathers are using leisure as a context to engage more with their children and fulfil the social expectation of being a good dad.
In exploring the changing position of children in family leisure, the second paper shows that the photographs provide evidence of a shift away from children as observers and followers of
family leisure in the early twentieth century, to being more under control in the post-war years, to being recognised as important social agents through the 1970s, to their current position as active decision makers in family leisure.
Finally, in an investigation into gender roles in family leisure food provisioning, the third paper finds that despite social changes contributing to the empowerment of women, they still carry the main responsibility for the facilitation of food-related chores in the leisure experience. While men take the ‘frontstage glory’ of food preparation during family leisure occasions, women are shown either in the kitchen alone or looking after small children, doing the ‘backstage work’.
Studying the changing nature of family life through time provides valuable insights regarding family relationships and how they have changed in relation to evolving social norms and patterns. However, it must be remembered that social values linked to the meanings ascribed to families are place specific and, as a result, the findings highlighted in this thesis cannot simply be assumed to be the same across the world. Looking forward then, it is important that the research on which this thesis is based is expanded into different cultural settings. In addition, this study provides an opportunity to consider the value of visual archival material and how this data can inform leisure studies
Spring Meal Plans
No full textEight sets of meal plans, which are designed to feed a flat of four students five dinner meals per week. The meals are healthy, affordable, and zero-waste. As well as recipes and shopping lists, the meal plans contain helpful information such as nutrition information, the cost per serving and food waste reduction tips
